148 research outputs found
Backdoor Attacks Against Incremental Learners: An Empirical Evaluation Study
Large amounts of incremental learning algorithms have been proposed to
alleviate the catastrophic forgetting issue arises while dealing with
sequential data on a time series. However, the adversarial robustness of
incremental learners has not been widely verified, leaving potential security
risks. Specifically, for poisoning-based backdoor attacks, we argue that the
nature of streaming data in IL provides great convenience to the adversary by
creating the possibility of distributed and cross-task attacks -- an adversary
can affect \textbf{any unknown} previous or subsequent task by data poisoning
\textbf{at any time or time series} with extremely small amount of backdoor
samples injected (e.g., based on our observations). To attract the
attention of the research community, in this paper, we empirically reveal the
high vulnerability of 11 typical incremental learners against poisoning-based
backdoor attack on 3 learning scenarios, especially the cross-task
generalization effect of backdoor knowledge, while the poison ratios range from
to as low as . Finally, the defense mechanism based on activation
clustering is found to be effective in detecting our trigger pattern to
mitigate potential security risks
Methylation-mediated silencing of PTPRD induces pulmonary hypertension by promoting pulmonary arterial smooth muscle cell migration via the PDGFRB/PLCγ1 axis
OBJECTIVE: Pulmonary hypertension is a lethal disease characterized by pulmonary vascular remodeling and is mediated by abnormal proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs). Platelet-derived growth factor BB (PDGF-BB) is the most potent mitogen for PASMCs and is involved in vascular remodeling in pulmonary hypertension development. Therefore, the objective of our study is to identify novel mechanisms underlying vascular remodeling in pulmonary hypertension.
METHODS: We explored the effects and mechanisms of PTPRD downregulation in PASMCs and PTPRD knockdown rats in pulmonary hypertension induced by hypoxia.
RESULTS: We demonstrated that PTPRD is dramatically downregulated in PDGF-BB-treated PASMCs, pulmonary arteries from pulmonary hypertension rats, and blood and pulmonary arteries from lung specimens of patients with hypoxic pulmonary arterial hypertension (HPAH) and idiopathic PAH (iPAH). Subsequently, we found that PTPRD was downregulated by promoter methylation via DNMT1. Moreover, we found that PTPRD knockdown altered cell morphology and migration in PASMCs via modulating focal adhesion and cell cytoskeleton. We have demonstrated that the increase in cell migration is mediated by the PDGFRB/PLCγ1 pathway. Furthermore, under hypoxic condition, we observed significant pulmonary arterial remodeling and exacerbation of pulmonary hypertension in heterozygous PTPRD knock-out rats compared with the wild-type group. We also demonstrated that HET group treated with chronic hypoxia have higher expression and activity of PLCγ1 in the pulmonary arteries compared with wild-type group.
CONCLUSION: We propose that PTPRD likely plays an important role in the process of pulmonary vascular remodeling and development of pulmonary hypertension in vivo
Circulating Mucosal-Associated Invariant T Cells in a Large Cohort of Healthy Chinese Individuals From Newborn to Elderly
Mucosal-associated invariant T (MAIT) cells, which are enriched in human blood and express a semi-invariant TCR chain, play important roles in conditions such as infectious diseases and cancer. The influence of age on levels and functional characteristics of circulating MAIT cells have not been fully addressed. Here we have collected blood samples from a large cohort of healthy Chinese individuals from newborn (cord blood) to the elderly and assessed the levels of circulating MAIT cells as well as their phenotype, activation and apoptosis status, and cytokine expression profiles after in vitro stimulation. We found that the frequencies of circulating MAIT cells gradually increased in blood from newborns as they progressed into adulthood (20–40 years old) but then decreased during further progression toward old age (>60 years old). The lowered numbers of circulating MAIT cells in the elderly was correlated with a gradual increase of apoptosis. A majority of circulating MAIT cells expressed the chemokine receptors CCR5 and CCR6, and most also expressed CD8 and CD45RO. Few expressed CD69 in cord blood, but the frequency increased with age. Upon in vitro activation with PMA plus ionomycin or IL12 plus IL18, fewer MAIT cells isolated from the young adult group expressed IFN-γ, IL17A and Granzyme B then cells from other age groups while the proportion of cells that expressed TNF-α was similar. Taken together, our data provide information for guiding the assessment of normal levels and phenotypes of MAIT cells at different ages in healthy individuals and patients
Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy
Emerging evidence suggests that CNS injury and neurocognitive impairment persist in the setting of chronic HIV infection and combination antiretroviral therapy (CART). Yet whether neurological injury can progress in this setting remains uncertain
Evaluation of Tolerability, Pharmacokinetics and Pharmacodynamics of Vicagrel, a Novel P2Y12 Antagonist, in Healthy Chinese Volunteers
Background: Vicagrel is a novel anti-platelet drug and hydrolyzed to the same intermediate as clopidogrel via esterase, instead of CYP2C19. Here we report the first clinical trial on the tolerability, pharmacokinetics and pharmacodynamics of different doses of vicagrel, and comparison with clopidogrel in healthy Chinese volunteers.Methods: This study was conducted in two parts. Study I was a dose-escalating (5–15 mg) study. For each dose, 15 participants were randomized into three groups (total n = 45); nine participants were given vicagrel, three were given clopidogrel, and three were given a placebo. Study II was conducted to assess interactions between vicagrel and aspirin in 15 healthy participants. The plasma concentrations of the metabolites of vicagrel and clopidogrel were determined using a LC-MS/MS method. Platelet aggregation was assessed using the VerifyNow-P2Y12 assay.Results: Vicagrel (5–15 mg per day) dosing for 10 days or addition of aspirin was well tolerated in healthy volunteers. The exposure of the active metabolite increased proportionally across the dose range and was higher (~10-fold) than clopidogrel. The levels of IPA dosing 75 mg clopidogrel were between the responses of 5 mg and 10 mg vicagrel. After a single loading dose of vicagrel (30 mg) and a once-daily maintenance dose (7.5 mg) for 8 days, the maximum inhibition of platelet aggregation was similar to that seen with the combined use of vicagrel and aspirin (100 mg/day).Conclusion: Oral vicagrel demonstrated a favorable safety profile and excellent anti-platelet activity, which could be a promising P2Y12 antagonist as anti-platelet drug and can be further developed in phase II/III studies, and marketing for the unmet medical needs of cardiovascular diseases. The study was registered at http://www.chictr.org.cn (ChiCTR-IIR-16009260)
Recent approaches in designing bioadhesive materials inspired by mussel adhesive protein
Marine mussels secret protein-based adhesives, which enable them to anchor to various surfaces in a saline, intertidal zone. Mussel foot proteins (Mfps) contain a large abundance of a unique, catecholic amino acid, Dopa, in their protein sequences. Catechol offers robust and durable adhe-sion to various substrate surfaces and contributes to the curing of the adhesive plaques. In this article, we review the unique features and the key functionalities of Mfps, catechol chemistry, and strategies for preparing catechol-functionalized poly- mers. Specifically, we reviewed recent findings on the contributions of various features of Mfps on interfacial binding, which include coacervate formation, surface drying properties, control of the oxidation state of catechol, among other features. We also summarized recent developments in designing advanced biomimetic materials including coacervate-forming adhesives, mechanically improved nano- and micro-composite adhesive hydrogels, as well as smart and self-healing materials. Finally, we review the applications of catechol-functionalized materials for the use as biomedical adhesives, therapeutic applications, and antifouling coatings
Golden single-atomic-site platinum electrocatalysts
Bimetallic nanoparticles with tailored structures constitute a desirable model system for catalysts, as crucial factors such as geometric and electronic effects can be readily controlled by tailoring the structure and alloy bonding of the catalytic site. Here we report a facile colloidal method to prepare a series of platinum–gold (PtAu) nanoparticles with tailored surface structures and particle diameters on the order of 7 nm. Samples with low Pt content, particularly Pt 4 Au 96 , exhibited unprecedented electrocatalytic activity for the oxidation of formic acid. A high forward current density of 3.77 A mg Pt −1 was observed for Pt 4 Au 96 , a value two orders of magnitude greater than those observed for core–shell structured Pt 78 Au 22 and a commercial Pt nanocatalyst. Extensive structural characterization and theoretical density functional theory simulations of the best-performing catalysts revealed densely packed single-atom Pt surface sites surrounded by Au atoms, which suggests that their superior catalytic activity and selectivity could be attributed to the unique structural and alloy-bonding properties of these single-atomic-site catalysts
Neuroimaging Feature Terminology: A Controlled Terminology for the Annotation of Brain Imaging Features
System-Theoretic Process Analysis Based on SysML/MARTE and NuSMV
Systems Theoretical Accident Model and Process (STAMP), which considers system safety as an emergent property of the system, is a more effective accident/loss causality model for modern complex systems. Based on STAMP, System Theoretical Process Analysis (STPA) has attracted increasing attention as a new approach to hazard analysis, and relevant international standards are being developed. However, STPA is mainly performed manually, leading to inefficiencies, and constructs models in non-standard language, hindering the integration with existing systems engineering. STPA-SN (STPA based on SysML/MARTE and NuSMV) is proposed to build model in SysML, describing the timing with MARTE (Modeling and Analysis of Real-Time and Embedded Systems), transform SysML model into NuSMV model and output loss scenarios automatically with model checker. An application example of STPA-SN is provided to demonstrate potentials for higher efficiency of analysis and for collaboration with SysML-based systems engineering
System-Theoretic Process Analysis Based on SysML/MARTE and NuSMV
Systems Theoretical Accident Model and Process (STAMP), which considers system safety as an emergent property of the system, is a more effective accident/loss causality model for modern complex systems. Based on STAMP, System Theoretical Process Analysis (STPA) has attracted increasing attention as a new approach to hazard analysis, and relevant international standards are being developed. However, STPA is mainly performed manually, leading to inefficiencies, and constructs models in non-standard language, hindering the integration with existing systems engineering. STPA-SN (STPA based on SysML/MARTE and NuSMV) is proposed to build model in SysML, describing the timing with MARTE (Modeling and Analysis of Real-Time and Embedded Systems), transform SysML model into NuSMV model and output loss scenarios automatically with model checker. An application example of STPA-SN is provided to demonstrate potentials for higher efficiency of analysis and for collaboration with SysML-based systems engineering
- …